Lowest Rates of Discontinuation Observed With Galcanezumab Among Self-Injectable CGRP Monoclonal Antibodies

Author(s):

When comparing galcanezumab, fremanezumab, and erenumab, 3 FDA-approved CGRP medications for preventive migraine, time to switch was lowest for erenumab and similar for galcanezumab and fremanezumab.

Oralee J. Varnado, PhD

In a real-world study of individuals using self-injectable calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments, results over a 12-month period showed that discontinuation rates were lowest among those treated with galcanezumab (Emgality; Eli Lilly). Most patients switched to onabotulinumtoxinA, topiramate, or a difference CGRP mAb.¹

The retrospective cohort study, presented at the 2023 American Headache Society (AHS) Annual Meeting, held June 15-18, in Austin, Texas, used administrative claims data on individuals with at least 1 claim for a self-injectable CGRP mAb of either galcanezumab, fremanezumab (Ajovy; Teva Pharmaceuticals), or erenumab (Aimovig; Amgen). Over the 12-month post-index period, approximately half of the patients discontinued their index drug: galcanezumab initiators (47.8%), fremanezumab initiators (52.5%), and erenumab initiators (52.5%).

Presented by Oralee J. Varnado, PhD, research advisor, Eli Lilly, the study included 9121 patients initiating galcanezumab, 5003 fremanezumab, and 12,052 erenumab between May 2018 and September 2020. The study excluded those with claims for more than 1 CGRP mAb on their index date, as well as those with evidence of cluster headache and those who received index drug class during the 12-month pre-index period. Discontinuation was defined as failure to refill the index drug within 60 days after depletion of the days’ supply from previous fills.

Following discontinuation of their index drug, 49.9% of galcanezumab initiators, 51.9% of fremanezumab initiators, and 57.4% of erenumab initiators, switched to another preventive therapy. Galcanezumab initiators had the longest median days to switch (181.0), followed by the fremanezumab (180.0) and erenumab (170.0) groups. Among the 31.7% of erenumab initiators who changed their dose during the 12-month follow-up period, 85.0% increased their dose from 70 to 140 mg.

Among patients who switched, the CGRP and non-CGRP preventive therapies used varied across groups. For galcanezumab, patients mostly switched to ontabotulinumtoxinA (18.9%), followed by topiramate (17.7%), erenumab (14.1%), and fremanezumab (8.5%). OntabotulinumtoxinA continued to be the most switched to medication for those on fremanezumab (18.3%), followed by galcanezumab (15.2%), topiramate (15.1%), and erenumab (13.4%). As for erenumab initiators, galcanezumab (22.7%) was the most switched to medication, with onabotulinumtoxinA (18.4%), topiramate (13.7%), and fremanezumab (11.0%) rounding out the rest.

Galcanezumab was first approved by the FDA in September 2018 for the preventive treatment of migraine in adults, and later had its indication expanded in 2019 to include the treatment of episodic cluster headache. With the decision, it became the first marketed medication specific to treat cluster headache, a rare form of headache that produces extreme pain and tends to occur in clusters, often at the same time(s) of the day, for several weeks to months.²

Fremanezumab, a fully-humanized mAb that selectively targets CGRP, received FDA approval in September 2018 for the prevention of migraine in adults. It was originally approved as a prefilled syringe indicated for 1-time use; however, the FDA approved an autoinjector for the delivery of fremanezumab in January 2020, joining erenumab and galcanezumab as the anti-CGRP agents on the market available for administration via autoinjector.³

Although there are several reasons as to why patients switch off CGRP-targeting therapies, data has shown that patients may be at increased for migraine frequency and disability following treatment interruption or discontinuation. In a recently published longitudinal cohort study of patients on CGRP antibodies for at least 8 months, the benefits of migraine prophylaxis with CGRP mAbs were significantly reduced after 3 months of a drug holiday. Lead investigator Uwe Reuter, MD, PhD, and colleagues concluded that, “a discontinuation attempt should be carefully discussed with patients on successful CGRP mAbs therapy on an individual basis."⁴

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REFERENCES
1. Varnado O, Brady LB, Zagar A, Robles Y, Hoyt M. Discontinuation and switching patterns in patients with migraine initiating calcitonin gene-related peptide monoclonal antibodies: a US real-world study. Presented at: 2023 AHS Annual Meeting; June 15-18; Austin, TX.
2. FDA approves first treatment for episodic cluster headache that reduces the frequency of attacks. News release. FDA. June 4, 2019. Accessed June 15, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-episodic-cluster-headache-reduces-frequency-attacks

3. Teva announces FDA approval of ajovy (fremanezumab-vfrm) injection autoinjector. News release. Teva Pharmaceuticals. January 28, 2020. Accessed June 15, 2023. http://www.businesswire.com/news/home/20200128005810/en

4. Raffaelli B, Terhart M, Overeem LH, et al. Migraine evolution after the cessation of CGRP(receptor) antibody prophylaxis: a prospective, longitudinal cohort study. Cephalagia. 2022;42(4-5):326-334. doi:10.1177/03331024211046617